tbuckley/cabot-search huggingface dataset:
P51 A national analysis of demographic features associated with spindle cell melanoma
Authors: Xinxin Wu, Mohammed Al Kurnas, Adam Liu, Peter Silberstein
Journal: British Journal of Dermatology (2023)

Abstract Spindle cell melanoma (SCM) is a rare morphological subtype of melanoma, characterized histologically by atypical, spindled, malignant melanocytes (Weissinger SE, Keil P, Silvers DN et al. A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma. Mod Pathol 2014; 27:524–34). SCM often manifests as a broad metastatic illness, is frequently amelanotic and can arise nearly anywhere on the body, making diagnosis challenging (Xu Z, Shi P, Yibulayin F et al. Spindle cell melanoma: incidence and survival, 1973–2017. Oncol Lett 2018; 16:5091–9). Given the rarity of SCM, the epidemiology is not yet well explored. The National Cancer Database (NCDB) is a nationwide oncology outcome database for &amp;gt; 1500 commission-accredited cancer programmes in the US and Puerto Rico. This study aimed to investigate the demographic factors associated with patients diagnosed with SCM by analysis of the NCDB. A retrospective cohort analysis utilizing data from the NCDB from 2004 to 2020 included patients diagnosed with histologically confirmed SCM (n = 7556). Sociodemographic factors (sex, age, race, Hispanic status, insurance type, urban/rural designation, facility location, facility type, education, income, distance from residence to facility and Charlson–Deyo score) were analysed using Pearson χ2-tests, and multivariate analysis was performed via binary logistic regression. Since 2004, an average (SD) of 480.8 (63.7) cases have been diagnosed annually. Most patients were male (66.5%), White (97.6%), not Hispanic (95.2%) and insured by Medicare (56.3%) and lived in an urban area (98.5%). Mean (SD) age at diagnosis was 67.9 (14.5) years, with an average (SD) Charlson–Deyo comorbidity score of 0.3 (0.6) and a mean (SD) distance of 37.3 (113.4) miles from the patient’s residence to the hospital. The most common primary site for SCM was the skin of the upper limb and shoulder (22.6%), followed by skin of the scalp and neck (19.0%), skin of other and unspecified parts of face (17.9%), and skin of the trunk (17.3%). On multivariate analysis, males were more likely than females to be diagnosed at an older age [69.3 vs. 65.3 years, 95% confidence interval (CI) 0.979–0.990; P &amp;lt; 0.001], receive treatment at an academic facility (45.9% vs. 42.7%, 95% CI 1.018–1.270; P = 0.023) and have a Charlson–Deyo score of ≥ 3 (2.1% vs. 1.3%, 95% CI 0.374–0.924; P = 0.21). Given the lack of literature on SCM, this study serves as a valuable tool for understanding the demographic factors associated with the diagnosis. Future studies within the laboratory aim to determine the effect of these factors on overall survival with propensity score matching for other variables to identify disparities.
P76 Management of aciclovir-resistant mucocutaneous herpes simplex virus infection: a systematic review
Authors: Herbert Castillo Valladares, Nora Rudd, Kieron Leslie
Journal: British Journal of Dermatology (2023)

Abstract Aciclovir resistance results in immunocompromised hosts due to long-term antiviral therapy and ongoing viral replication. Aciclovir resistance in herpes simplex virus (HSV) poses a major concern, as this can lead to chronic and recalcitrant infection that significantly impacts on the quality of life. While different treatment options exist, there are currently no standardized clinical treatment guidelines for mucocutaneous aciclovir-resistant (ACV-R) HSV infection. This systematic review seeks to identify safe and effective treatments for mucocutaneous ACV-R HSV infection. For this systematic review, PubMed/MEDLINE and Embase were searched in September 2022 for all articles published between 1 January 1980 and 1 September 2022. Studies were included if they described the use of a medication for the treatment of mucocutaneous ACV-R HSV infection. From the initial search that yielded 1066 studies, 86 met the inclusion criteria and were selected. Of the 86 studies, 6 were clinical trials and 80 were case reports/series. A total of 318 patients were included in our review. Foscarnet [intravenous (IV) and topical] was studied in 5 clinical trials and 25 case reports/series, leading to complete response in most patients, with adverse effects including renal toxicity and electrolyte abnormalities. Vidarabine (IV) was found to be inferior to foscarnet in a clinical trial and reported in two case reports. Common side-effects included nausea, anaemia and renal impairment. Trifluridine (topical) was studied in a clinical trial and a case report, showing complete response in some patients. Cidofovir (IV, topical, intralesional) was studied in 21 case reports/series, showing complete response in most patients, with renal impairment as the most common adverse effect. Imiquimod (topical) was studied in eight case reports/series, showing complete response and no side-effects. Pritelivir (oral) was reported in two case reports/series, showing complete response and no side-effects. Combination treatment was reported in 10 case reports/series with variable clinical response. Our review also identified reports of less widely used treatments. These include artesunate, zidovudine, varicella-zoster virus vaccine, leflunomide and surgical excision, which achieved variable response rates but have not been widely studied. While foscarnet and cidofovir have the most robust evidence, IV administration of these agents is associated with significant side-effects and may be limiting. Intralesional and topical formulations of cidofovir, trifluridine and imiquimod are alternative options appropriate for outpatient management. Pritelivir is a novel and promising treatment of mucocutaneous ACV-R HSV infection.
Author Correction: Skin chronological aging drives age-related bone loss via secretion of cystatin-A
Authors: Wenquan Liang, Qingjing Chen, Shasha Cheng, Ruiming Wei, Yuejun Li, Chenfeng Yao, Zhicong Ouyang, Dawei Kang, Ajuan Chen, Zezheng Liu, Kai Li, Xiaochun Bai, Qingchu Li, Bin Huang
Journal: Nature Aging (2023)
Real-world data of long-term survival in patients with T-cell lymphoma who underwent stem cell transplantation
Authors: Dong Won Baek, Joon Ho Moon, Jae Hoon Lee, Ka-Won Kang, Ho Sup Lee, Hyeon-Seok Eom, Enuyoung Lee, Ji Hyun Lee, Jeong-Ok Lee, Seong Kyu Park, Seok Jin Kim, Keon Hee Yoo, Sung-Soo Yoon, Youngil Koh, Hyoung Jin Kang, Jong-Ho Won, Chuhl Joo Lyu, Seung Min Hahn, Jung-Hee Lee, Joon Seong Park, Jae-Cheol Jo, Yeung-Chul Mun, Deok-Hwan Yang, Ga-Young Song, Sung-Nam Lim, Sang Kyun Sohn
Journal: Blood Cancer Journal (2023)

This study aimed to identify the benefits of autologous-stem cell transplantation (auto-SCT) and allogeneic-SCT (allo-SCT) in patients with aggressive T-cell lymphomas to aid in the selection of transplantation type in clinical practice. This study retrospectively analyzed data from 598 patients who underwent transplantation for T-cell lymphomas from 2010 to 2020. In total, 317 patients underwent up-front SCT as consolidation therapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 68.7% and 76.1%, respectively. Patients who underwent auto-SCT had significantly better OS (p = 0.026) than those who underwent allo-SCT; however, no statistical difference in PFS was found. Transplantation was used as a salvage therapy in 188 patients who had relapsed/refractory disease. Overall, 96 (51.1%) patients underwent auto-SCT and 92 (48.9%) patients underwent allo-SCT. Auto-SCT improved long-term survival in patients with complete remission (CR). Allo-SCT demonstrated better 3-year PFS in patients with partial remission and relapsed/refractory disease status. However, >50% of patients died within 1 year of allo-SCT. As a consolidative therapy, up-front auto-SCT demonstrated a survival benefit. Auto-SCT was also effective in patients who achieved CR after salvage therapy. If the disease persists or cannot be controlled, allo-SCT may be considered with reduced intensity conditioning.
Abstract 9992: Urine Proteome Analysis Allows Establishment of Polypeptide Patterns non-Invasively Reflecting Drug-Mediated Regression of Atherosclerosis in ApoE-/--Mice
Authors: Constantin Von Zur Muhlen, Eric Schiffer, Christine Sackmann, YC Chen, Petra Zúrbig, Harald Mischak, Christoph Bode, Karlheinz Peter
Journal: Circulation (2012)

Background: Recently, non-invasive urine proteome analysis established a multimarker proteome approach towards non-invasive detection of atherosclerosis in an ApoE-/--mouse model, and relevance of this proteome pattern was also confirmed in human atherosclerosis. Urine was used since it lacks peptidase activity, which is found in blood and could falsify proteome analysis. Additionally, non-invasive monitoring of anti-atherosclerotic therapy with statins is of high clinical interest, and could be an important tool for guiding medical therapy. We therefore aimed to identify urinary polypeptides reflecting statin therapy in the ApoE-/--mouse model. Methods and Results: Urine of ApoE-/--mice either on high fat diet (HFD) or chow diet (CD) was collected over 15 weeks; each group was divided into subgroups with or without statin therapy applied by oral gavaging (HFD+S and HFD-S). Capillary electrophoresis mass spectrometry (CE-MS) of urine samples identified 5 polypeptides specifically reflecting statin treatment, resulting in a shift towards a more “healthy” polypeptide pattern until week 12. Sequencing of the discovered polypeptides identified fragments of α1-antitrypsin, EGF, kidney androgen regulated protein (KAP) and napsin. In histology, plaque size was significantly reduced by statin treatment, and presence of marker proteins in atherosclerotic plaques was confirmed by immunohistochemistry. Furthermore, urinary excretion levels of α1-antitrypsin fragments significantly correlated with intraplaque α1-antitrypsin content, mirroring plaque protein expression in the urine proteome. Conclusions: Urine proteome analysis allows discovery of novel biomarkers for the non-invasive monitoring of an anti-atherosclerotic therapy with statins in an ApoE-/--mouse model. The established multimarker proteome pattern reflects regression of plaque size in histology, and marker excretion levels also correlate with their expression in immunohistochemistry. This approach allows monitoring of atherosclerosis progression and statin treatment in mice, and thus promises to be an important and clinically relevant tool for monitoring and guiding of established but even more so of novel developments of anti-atherosclerotic drugs.
From function to translation: Decoding genetic susceptibility to human diseases via artificial intelligence
Authors: Erping Long, Peixing Wan, Qingyu Chen, Zhiyong Lu, Jiyeon Choi
Journal: Cell Genomics (2023)

While genome-wide association studies (GWAS) have discovered thousands of disease-associated loci, molecular mechanisms for a considerable fraction of the loci remain to be explored. The logical next steps for post-GWAS are interpreting these genetic associations to understand disease etiology (GWAS functional studies) and translating this knowledge into clinical benefits for the patients (GWAS translational studies). Although various datasets and approaches using functional genomics have been developed to facilitate these studies, significant challenges remain due to data heterogeneity, multiplicity, and high dimensionality. To address these challenges, artificial intelligence (AI) technology has demonstrated considerable promise in decoding complex functional datasets and providing novel biological insights into GWAS findings. This perspective first describes the landmark progress driven by AI in interpreting and translating GWAS findings and then outlines specific challenges followed by actionable recommendations related to data availability, model optimization, and interpretation, as well as ethical concerns.
Treatment of Idiopathic Recurrent Pericarditis With Goflikicept
Authors: Valentina Yu. Myachikova, Alexey L. Maslyanskiy, Olga M. Moiseeva, Oksana V. Vinogradova, Ekaterina V. Gleykina, Yan Lavrovsky, Antonio Abbate, Sergey A. Grishin, Alina N. Egorova, Margarita L. Schedrova, Mikhail Yu. Samsonov
Journal: Journal of the American College of Cardiology (2023)
Cognitive Behavioral Therapy Improves Quality of Life in Patients With Symptomatic Paroxysmal Atrial Fibrillation
Authors: Josefin Särnholm, Helga Skúladóttir, Christian Rück, Erland Axelsson, Marianne Bonnert, Maria Bragesjö, Ashwin Venkateshvaran, Eva Ólafsdóttir, Susanne S. Pedersen, Brjánn Ljótsson, Frieder Braunschweig
Journal: Journal of the American College of Cardiology (2023)
Single Troponin Measurement to Rule Out Myocardial Infarction
Authors: Allan S. Jaffe, Richard Body, Nicholas L. Mills, Kristin M. Aakre, Paul O. Collinson, Amy Saenger, Ole Hammarsten, Ryan Wereski, Torbjørn Omland, Yader Sandoval, Jordi Ordonez-Llanos, Fred S. Apple
Journal: Journal of the American College of Cardiology (2023)
Prostatic artery embolisation versus medical treatment in patients with benign prostatic hyperplasia (PARTEM): a randomised, multicentre, open-label, phase 3, superiority trial
Authors: Marc Sapoval, Nicolas Thiounn, Aurélien Descazeaud, Carole Déan, Alain Ruffion, Gaële Pagnoux, Ricardo Codas Duarte, Grégoire Robert, Francois Petitpierre, Gilles Karsenty, Vincent Vidal, Thibaut Murez, Hélène Vernhet-Kovacsik, Alexandre de la Taille, Hicham Kobeiter, Romain Mathieu, Jean-Francois Heautot, Stéphane Droupy, Julien Frandon, Nicolas Barry Delongchamps, Virginie Korb-Savoldelli, Isabelle Durand-Zaleski, Helena Pereira, Gilles Chatellier, Olivier Pellerin, Brigitte Sabatier, Charles Dariane, Benjamin Gabay, Paul Cezar Moldovan, Olivier Rouvière, Jean Champagnac, Samuel Lagabrielle, Nicolas Grenier, Romain Boissier, Éric Lechevallier, Jalal-Jean Izaaryene, Farouk Tradi, Raphaele Arrouasse, Julien Defontaines, Xavier Joseph, Philippe Le Corvoisier, Emilie Sbidian, Cécile Champy, Mélanie Chiaradia, Armand Chevrot, Cyrille Blion, Jean Goupil, Julie Bulsei, Alexandra Vappereau
Journal: The Lancet Regional Health - Europe (2023)

Prostatic artery embolisation (PAE) is a minimally invasive treatment of symptomatic benign prostatic hyperplasia (BPH). Our aim was to compare patient's symptoms improvement after PAE and medical treatment. A randomised, open-label, superiority trial was set in 10 French hospitals. Patients with bothersome lower urinary tract symptoms (LUTS) defined by International Prostatic Symptom Score (IPSS) > 11 and quality of life (QoL) > 3, and BPH ≥50 ml resistant to alpha-blocker monotherapy were randomly assigned (1:1) to PAE or Combined Therapy ([CT], oral dutasteride 0.5 mg/tamsulosin hydrochloride 0.4 mg per day). Randomisation was stratified by centre, IPSS and prostate volume with a minimisation procedure. The primary outcome was the 9-month IPSS change. Primary and safety analysis were done according to the intention-to-treat (ITT) principle among patients with an evaluable primary outcome. ClinicalTrials.gov Identifier: NCT02869971. Ninety patients were randomised from September 2016 to February 2020, and 44 and 43 patients assessed for primary endpoint in PAE and CT groups, respectively. The 9-month change of IPSS was -10.0 (95% confidence interval [CI]: -11.8 to -8.3) and -5.7 (95% CI: -7.5 to -3.8) in the PAE and CT groups, respectively. This reduction was significantly greater in the PAE group than in the CT group (-4.4 [95% CI: -6.9 to -1.9], p = 0.0008). The IIEF-15 score change was 8.2 (95% CI: 2.9-13.5) and -2.8 (95% CI: -8.4 to 2.8) in the PAE and CT groups, respectively. No treatment-related AE or hospitalisation was noticed. After 9 months, 5 and 18 patients had invasive prostate re-treatment in the PAE and CT group, respectively. In patients with BPH ≥50 ml and bothersome LUTS resistant to alpha-blocker monotherapy, PAE provides more urinary and sexual symptoms benefit than CT up to 24 months. French Ministry of Health and a complementary grant from Merit Medical.
Transcriptome- and proteome-wide association studies nominate determinants of kidney function and damage
Authors: Pascal Schlosser, Jingning Zhang, Hongbo Liu, Aditya L. Surapaneni, Eugene P. Rhee, Dan E. Arking, Bing Yu, Eric Boerwinkle, Paul A. Welling, Nilanjan Chatterjee, Katalin Susztak, Josef Coresh, Morgan E. Grams
Journal: Genome biology (2023)

The pathophysiological causes of kidney disease are not fully understood. Here we show that the integration of genome-wide genetic, transcriptomic, and proteomic association studies can nominate causal determinants of kidney function and damage.
High-resolution feature based central venous catheter tip detection network in X-ray images
Authors: Yuhan Wang, Hak Keung Lam, Zeng-Guang Hou, Rui-Qi Li, Xiao-Liang Xie, Shi-Qi Liu
Journal: Medical Image Analysis (2023)

Hospital patients can have catheters and lines inserted during the course of their admission to give medicines for the treatment of medical issues, especially the central venous catheter (CVC). However, malposition of CVC will lead to many complications, even death. Clinicians always detect the malposition based on position detection of CVC tip via X-ray images. To reduce the workload of the clinicians and the percentage of malposition occurrence, we propose an automatic catheter tip detection framework based on a convolutional neural network (CNN). The proposed framework contains three essential components which are modified HRNet, segmentation supervision module, and deconvolution module. The modified HRNet can retain high-resolution features from start to end, ensuring the maintenance of precise information from the X-ray images. The segmentation supervision module can alleviate the presence of other line-like structures such as the skeleton as well as other tubes and catheters used for treatment. In addition, the deconvolution module can further increase the feature resolution on the top of the highest-resolution feature maps in the modified HRNet to get a higher-resolution heatmap of the catheter tip. A public CVC Dataset is utilized to evaluate the performance of the proposed framework. The results show that the proposed algorithm offering a mean Pixel Error of 4.11 outperforms three comparative methods (Ma's method, SRPE method, and LCM method). It is demonstrated to be a promising solution to precisely detect the tip position of the catheter in X-ray images.
4-1BB-4-1BBL cis-interaction contributes to the survival of self-reactive CD8+ T cell
Authors: Eunjung Cho, Rohit Singh, Chungyong Han, Seon-Hee Kim, Kwang H. Kim, Bo-Mi Park, Dong Hoon Shin, Seongeun Han, Young H. Kim, Byoung S. Kwon, Ki Taek Nam, Beom K. Choi
Journal: Cellular and Molecular Immunology (2023)
A reappraisal of ASXL1 mutation sites and the cohesin-binding motif in myeloid disease
Authors: Steven M. Johnson, James Haberberger, Jonathan Galeotti, Lori Ramkissoon, Catherine C. Coombs, Daniel R. Richardson, Matthew C. Foster, Daniel Duncan, Joshua F. Zeidner, Naomi L. Ferguson, Nathan D. Montgomery
Journal: Blood Cancer Journal (2023)
The DNA methylation status of the TERT promoter differs between subtypes of mature B-cell lymphomas
Authors: Alexandra G. Kouroukli, Anja Fischer, Helene Kretzmer, Emil Chteinberg, Nivethika Rajaram, Selina Glaser, Julia Kolarova, Pavel Bashtrykov, Stephan Mathas, Hans G. Drexler, Hitoshi Ohno, Ole Ammerpohl, Albert Jeltsch, Reiner Siebert, Susanne Bens
Journal: Blood Cancer Journal (2023)
Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing
Authors: Hyatt Balke-Want, Vimal Keerthi, Nikolaos Gkitsas, Andrew G. Mancini, Gavin L. Kurgan, Carley Fowler, Peng Xu, Xikun Liu, Kyle Asano, Sunny Patel, Christopher J. Fisher, Annie K. Brown, Ramya H. Tunuguntla, Shabnum Patel, Elena Sotillo, Crystal L. Mackall, Steven A. Feldman
Journal: Molecular Cancer (2023)

Abstract Background Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to CAR-T cells is not adequate to meet clinical needs, in part due to high cost and long lead times for manufacturing clinical grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 and double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) via homology-directed repair (HDR), however yields with this approach have been limiting for clinical application (dsDNA) or access to large yields sufficient to meet the manufacturing demands outside early phase clinical trials is limited (ssDNA). Methods We applied homology-independent targeted insertion (HITI) or HDR using CRISPR/Cas9 and nanoplasmid DNA to insert an anti-GD2 CAR into the T cell receptor alpha constant (TRAC) locus and compared both targeted insertion strategies in our system. Next, we optimized post-HITI CRISPR EnrichMENT (CEMENT) to seamlessly integrate it into a 14-day process and compared our knock-in with viral transduced anti-GD2 CAR-T cells. Finally, we explored the off-target genomic toxicity of our genomic engineering approach. Results Here, we show that site directed CAR integration utilizing nanoplasmid DNA delivered via HITI provides high cell yields and highly functional cells. CEMENT enriched CAR T cells to approximately 80% purity, resulting in therapeutically relevant dose ranges of 5.5 × 10 8 –3.6 × 10 9 CAR + T cells. CRISPR knock-in CAR-T cells were functionally comparable with viral transduced anti-GD2 CAR-T cells and did not show any evidence of off-target genomic toxicity. Conclusions Our work provides a novel platform to perform guided CAR insertion into primary human T-cells using nanoplasmid DNA and holds the potential to increase access to CAR-T cell therapies.
Monitoring measurable residual disease and chimerism in patients with JAK2 V617F-positive myelofibrosis after allogeneic hematopoietic cell transplantation
Authors: Jong-Mi Lee, Ari Ahn, Eun Jeong Min, Sung-Eun Lee, Myungshin Kim, Yonggoo Kim
Journal: Blood Cancer Journal (2023)

Monitoring measurable residual disease and chimerism
Postprocedural Coronary Perfusion and Mortality in Patients With Acute Myocardial Infarction and Extracorporeal Cardiopulmonary Resuscitation
Authors: Takahiro Nakashima, Takayuki Otani, Shunichi Kato, Marina Arai, Akihiko Inoue, Toru Hifumi, Tetsuya Sakamoto, Yasuhiro Kuroda, Yoshio Tahara
Journal: Journal of the American College of Cardiology (2023)